Hypothalamic homeostatic and forebrain reward-related genes were examined in the context of scheduled meal feeding without caloric restriction in C57BL/6 mice. Mice fed ad libitum but allowed access to a palatable high fat diet (HFD) for 2h a day rapidly adapted their feeding behaviour and consumed approximately 80% of their daily energy intake during this 2h-scheduled feed. Gene expression levels were examined during either the first or second hour of scheduled feeding vs. 24h ad libitum feeding on the same HFD. Gene expression of NPY, AgRP, CART, POMC, OB-Rb and SOCS3 in the arcuate nucleus (ARC), and enkephalin, dynorphin, dopamine-2-receptor and dopamine-3-receptor in the nucleus accumbens (NAcc) were measured by in-situ hybridisation. Mice fed ad libitum on HFD had the highest energy intake, body weight gain, fat mass and serum leptin, whereas schedule-fed mice had a mild obese phenotype with intermediate energy intake, body weight gain, fat mass and serum leptin. The effects of feeding regime on ARC gene expression were emphasised by significant positive or negative correlations with body weight gain, fat mass and serum leptin concentration, but did not appear to be related to feeding behaviour in the schedule-fed groups, i.e. the large, binge-type meals. No potential candidates for the regulation of these meals were revealed, although an increase in vertical and horizontal activity prior to scheduled feeding indicated that schedule-fed mice display food anticipatory activity, a behaviour thought to reflect hunger as well as the motivation to eat. However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of involvement of these genes in regulating large meals. This complements our previous characterisation of ARC and NAcc genes in schedule-fed mice and rats, but still leaves open the fundamental question about underlying mechanisms of meal feeding in the palatable scheduled feeding model.